Dataset Information

In-depth Serum Proteomics in Psoriasis reveals novel biomarkers for disease activity and response to Traditional Chinese Medicine

ABSTRACT: demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers for psoriasis, suggesting a great potential for application in translation studies and precision medicine in psoriasis and other immune-mediated diseases

ORGANISM(S): Homo Sapiens

SUBMITTER: Tiannan Guo

PROVIDER: PXD013089 | iProX | Wed Mar 13 00:00:00 GMT 2019

REPOSITORIES: iProX

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In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine.

Xu Meng M Deng Jingwen J Xu Kaikun K Zhu Tiansheng T Han Ling L Yan Yuhong Y Yao Danni D Deng Hao H Wang Dan D Sun Yaoting Y Chang Cheng C Zhang Xiaomei X Dai Jiayu J Yue Liang L Zhang Qiushi Q Cai Xue X Zhu Yi Y Duan Hu H Liu Yuan Y Li Dong D Zhu Yunping Y Radstake Timothy R D J TRDJ Balak Deepak M W DMW Xu Danke D Guo Tiannan T Lu Chuanjian C Yu Xiaobo X

Theranostics 20190413 9

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. <b>Methods</b>: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combi ...[more]

PMID: 31131048

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Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.

Project description:BackgroundTraditional, complementary, and alternative medicine (TCAM) has attracted increasing attention in developed countries, but its mainstream status in China, the home of TCAM, is unclear. Over the period of 2004-2016, we analyze the health resources and health resource utilization of traditional medicine in traditional Chinese medicine (TCM) hospitals in China.MethodsOver 2004-2016, we obtained data from all TCM hospitals in all Chinese provinces to create a hospital-based, longitudinal dataset. TCM health resources and their utilization were measured by two outcome variables: (1) primary outcome variables comprising the proportion of TCM physicians, TCM pharmacists, revenue from TCM drugs, and TCM prescriptions and (2) the secondary outcome variables, as proxies of westernization for TCM hospitals, comprising the number of medical equipment above RMB 10,000 and the proportion of surgery in inpatient visits. We used linear regression models with hospital-fixed effects to analyze time trends for the outcome variables.ResultsThe number of public TCM hospitals remained stable from 2004 to 2016, while the number of private TCM hospitals increased from 294 in 2004 to 1560 in 2016. There was a small percentage increase in the proportion of TCM physicians (0.280%), TCM pharmacists (0.298%), and revenue from Chinese medicines (0.331%) and TCM prescriptions (1.613%) per hospital per year. Chinese drugs accounted for less than a half of the total drug prescriptions, and accordingly, just one-third of the drug revenue was from Chinese medicines at TCM hospitals. The proportions of physicians, pharmacists, revenue from Chinese drug sales, and traditional medicine prescriptions never reach the 60% benchmark target for mainstream in TCM hospitals. As proxies for Western medicine practices in TCM hospitals, the number of medical equipment above RMB 10,000 rapidly rose by over 13 percent per hospital per year, but the proportion of inpatient surgeries declined by 0.830 percentage points per hospital per year, reflecting a mixed trend in the use of Western medicine practices.ConclusionFor the 2004-2016 period, traditional medicine, although making progress towards the mainstream benchmark of 60% TCM services, was still not mainstream at TCM hospitals.

Dataset Information

In-depth Serum Proteomics in Psoriasis reveals novel biomarkers for disease activity and response to Traditional Chinese Medicine

Publications

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine.

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